THE HUMEN PERSPECTIVE

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THE HUMEN PERSPECTIVE

• Disorders Associated with G protein-Coupled
  Receptors

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• ??
• ??(adenoma)??????,?????????????????????,??????????
  ???????????

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• ??????????????,????,??????????????????????????????
  ???????,? ??????????????????????????

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• ???????????????????????,????,????????,??????(?4-
  13),???????????????????????

?4-13???????
5

• ???????????,???????,????????,????,???????????????
  ??????????????????????,???????????

6

• ?????????????????????,???????????????,??????,????
  ??,??????????????????????????????????,???????,????
  ????

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• ?????????,??????????????????????????,????????????
  ??????,?????????????????????,????????,????????????
  ?,??????

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thyroid adenoma (????)

• Mutations that lead to a gain of function.
• mutations have been found to cause a type of
  benign thyroid tumor, called an adenoma.

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• CNDI????????????????????.?????????????????????????
  ??????,???????????????.

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thyroid adenoma (????)

• Unlike normal thyroid cells that secrete thyroid
  hormone only in response to stimulation by the
  pituitary(???) hormone TSH(??????), the cell of
  these thyroid adenomas secrete large quantities
  of thyroid hormone without having to be
  stimulated by TSH (the receptor is said to act
  constitutively).
• How Does This Happen?

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• The TSH receptor in these cells contains an
  amino acid substitution that affects the
  structure of the third intracellular loop of the
  protein (mutations at sites 5 or 6).

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thyroid adenoma (????)
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• As a result of the mutation, the TSH receptor
  constitutively activates a G protein on its inner
  surface, sending a continual signal through the
  pathway that leads not only to excessive thyroid
  hormone secretion but to the excessive cell
  proliferation that causes the tumor.

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• This conclusion was verified by introducing
  the mutant gene into cultured cells that normally
  lack this receptor and demonstrating that the
  synthesis of the mutant protein and its
  incorporation into the plasma membrane led to the
  continuous production of cAMP in the genetically
  engineered cells.

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Adenoma is not an inherited disease !
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Thanks for your attention